New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus Penicillium antarcticum KMM 4685.

Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B ( 1 ), β-resoantarctines A-C ( 3 , 5 , 6 ) and 8-dehydro-β-resoantarctine A ( 4 ), together with known 14-hydroxyasperentin (5'-hydroxyasperentin) ( 2 ), were isolated from the ethyl acetate extract of the fungus Penicillium antarcticum KMM 4685 associated with the brown alga Sargassum miyabei . The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher's method, and the biogenetic pathways for compounds 3 - 6 were proposed. For the very first time, the relative configuration of the C-14 center of a known compound 2 was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites 3 - 6 were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds 3 , 4 and 5 exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells.